EP1707116B1 - Impedance spectroscopy system for ischemic mucosal damage monitoring in hollow viscous organs - Google Patents
Impedance spectroscopy system for ischemic mucosal damage monitoring in hollow viscous organs Download PDFInfo
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- EP1707116B1 EP1707116B1 EP06015389A EP06015389A EP1707116B1 EP 1707116 B1 EP1707116 B1 EP 1707116B1 EP 06015389 A EP06015389 A EP 06015389A EP 06015389 A EP06015389 A EP 06015389A EP 1707116 B1 EP1707116 B1 EP 1707116B1
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- electrodes
- catheter
- mucosa
- complex impedance
- impedance spectrum
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
- A61B5/053—Measuring electrical impedance or conductance of a portion of the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
- A61B5/053—Measuring electrical impedance or conductance of a portion of the body
- A61B5/0538—Measuring electrical impedance or conductance of a portion of the body invasively, e.g. using a catheter
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/42—Detecting, measuring or recording for evaluating the gastrointestinal, the endocrine or the exocrine systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/24—Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
- A61B5/25—Bioelectric electrodes therefor
- A61B5/279—Bioelectric electrodes therefor specially adapted for particular uses
- A61B5/28—Bioelectric electrodes therefor specially adapted for particular uses for electrocardiography [ECG]
- A61B5/283—Invasive
- A61B5/287—Holders for multiple electrodes, e.g. electrode catheters for electrophysiological study [EPS]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/72—Signal processing specially adapted for physiological signals or for diagnostic purposes
- A61B5/7235—Details of waveform analysis
- A61B5/7264—Classification of physiological signals or data, e.g. using neural networks, statistical classifiers, expert systems or fuzzy systems
Definitions
- the present invention relates to systems for monitoring and quantifying ischemic damage in tissues.
- the gastrointestinal mucosa is at great risk of ischemia in the critically ill, and its disruption has been shown to he the motor of multiple organ failure, a leading cause of death.
- Knowledge of the level of damage can help guide therapy, reversing moderate damage and/or preventing further complications.
- path A in FIG. 6 the status of a healthy person's mucosa changes little, if at all, over time.
- Path C shows how the damage level of an ill person's ischemic mucosa greatly increases over the course of several hours if unchecked.
- path B further damage can be arrested if the ischemic damage is detected and an appropriate course of treatment is undertaken.
- chemic mucosal damage in the gastrointestinal tract of the critically ill patient is chemic mucosal damage in the gastrointestinal tract of the critically ill patient.
- Impedance spectroscopy has been used to detect ischemia (a condition of inadequate blood flow and oxygen delivery to a given tissue) in biological tissues using different instrumental methods. Impedance spectroscopy differs from other impedance measurements (which have long been used for a variety of biomedical applications such as cardiac output estimation, body fat measurement, and plethismography) in that it involves multiple measurements over a range of frequencies that as a whole contain significantly more information of the structural and electrical properties of the sample.
- impedance measurements which have long been used for a variety of biomedical applications such as cardiac output estimation, body fat measurement, and plethismography
- U.S. Pat. No. 5,434,377 to Dzwoczyk et al teaches the assessment of ischemia in the myocardium
- Both probes carry two electrodes.
- the first probe located within an epithelial cavity of a subject electrically interacts with the second probe positioned in a blood vessel to measure the impedance of the tissues lying between the two probes.
- Another primary object of the present invention is to provide an impedance spectroscopy system and catheter for the continuous monitoring of the level of damage, of the gastric mucosa in critically ill patients.
- the claimed impedance spectroscopy system for monitoring ischemic mucosal damage in hollow viscous organs comprises a sensor catheter and an impedance spectrometer far electrically driving the catheter to obtain 8 complex impedance spectrum of tissue proximate the catheter.
- the complex impedance spectrum is used to determine the extent to which the tissue is damaged, as opposed to determining if the tissue is ischemic. More specifically, as mentioned above, ischemia is a condition of inadequate blood flow and oxygen delivery to a given tissue, which may or may not result in tissue, damage ( i.e , is chemic tissue can be undamaged, and vice versa). Thus, detecting tissue ischemia does not result in a measurement of tissue damage, and a different process, as implemented in the present invention, must be utilized to do so.
- the catheter which is configured to be inserted into any hollow viscous organ, comprises four Ag/AgCl electrodes positioned on an end tip of the catheter.
- the electrodes are functionally ring-shaped, and are coaxially spaced apart a short distance from one another.
- the outer two ring electrodes inject current into the tissue, and the inner two electrodes measure the resulting voltage.
- Leads, electrically connected to the electrodes extend along the wall of the catheter tubing or in a lumen portion of the tubing, and terminate at an interface plug suitable for connection to the impedance spectrometer.
- the impedance spectrometer causes the electrodes in the tip of the catheter to inject a current into the mucosal tissue at different frequencies, allowing for the measurement of the tissue's complex impedance spectrum.
- the spectrum contains information of the structural and metabolic status of the tissue, and can be used to quantify the level of damage. More specifically, the spectrum can be appropriately graphically plotted against the spectrum of normal tissue, allowing for a direct visual comparison by trained personnel, and, therefore, an indication or measurement of damage. Alternatively, a standard pattern recognition system or the like may be used to automatically analyze the complex impedance spectrum and quantify the severity of the mucosal injury.
- the catheters 12a-12d are generally similar, in that each one has four electrodes with annular side surfaces positioned at a distal end of the catheter.
- the catheter 12a comprises a flexible tube 14 and four generally cylindrical electrodes 16a-16d disposed at one end thereof.
- the electrodes 15a-16d are electrically connected, via leads 18a-18d extending up through the tube 14, to an impedance spectrometer 20 portion of the system 10.
- the spectrometer 20 is used in conjunction with a signal processing device 22, such as an appropriately-programmed general purpose computer, for processing the complex impedance spectrum to detect tissue damage.
- a signal processing device 22 such as an appropriately-programmed general purpose computer, for processing the complex impedance spectrum to detect tissue damage.
- the catheter is placed in one of a patient's hollow viscous organs 35, and current is injected by two of the electrodes 16a, 16d at a range of frequencies.
- the other two electrodes 16b, 16c measure the resulting voltage spectrum, which is subsequently processed and analyzed by the spectrometer 20 and signal processing device 22.
- FIGS. 2A-2C show a first embodiment of the catheter 12a.
- the catheter 12a comprises the flexible plastic tube 14 that can be inserted in any hollow viscous organ.
- the four electrodes 16a-16d that function as ionic-current-to-electronir-current transducers, such as Ag/AgCl electrodes.
- the electrodes are substantially identical.
- each has a cylindrical central portion 24 having a first diameter and an annular side surface, and two cylindrical extensions 26 attached to the ends of the central portion and coaxial therewith.
- the extensions 26 have a second, reduced diameter, and each electrode 16a-16d has an axial through-bore.
- the electrodes 16a-16d are spaced equally apart from one another along the distal tip of the catheter 12a, and are separated by spacers (short lengths of tubing) 27a-27d. As best seen in FIG. 2A , the annular side walls of the central portions 24 of the electrodes 16a-16d are the only portions thereof that are exposed to the outside of the catheter 12a. Thus, each electrode 16a-16d is ring-like in functionality, and the distal end of the catheter (with the electrodes) is generally radially symmetric. The catheter, therefore, will provide the same measurements regardless of its radial orientation in an organ.
- the diameters of the central electrode portions 24 are about the same as the outer diameter of the tube 14. This ensures that the outer surface of the catheter 12a is relatively smooth, e.g ., that it has no more than minor surface roughness or undulations.
- the electrodes 16a-16d are respectively electrically connected to the leads 18a-18d (via soldering, welding, or the like) in the electrodes' axial through-bores.
- the leads from the distal three electrodes 16b-16d extend through the axial through-bores of the other electrodes, as applicable.
- the electrodes 16a-16d, leads 18a-18d, and short portions of tubing are kept in place and stabilized via an epoxy or plastic fill 28.
- the catheter 12a may be a stand alone sensor catheter, or it may be provided as part of a feeding/sump tube or some other type of life support tube or catheter.
- the catheter 12a doubles as a feeding tube. More specifically, the end of the catheter 12a is provided with the electrodes 16a-16d, while the remainder of the tube 14 is left hollow to act as a feeding line 29.
- the catheter tube 14 may include a second lumen for sampling and feeding, like a Levin type gastric catheter, and/or a third lumen for a vented feeding/sump tube, as in a Salem type gastric catheter.
- the electrical leads 18a-18d extend drown through a side wall portion of the tube 14 having a vent lumen 30 and a feeding/ sump lumen 32.
- the leads 18a-18d are fed through the tube 14, if needed (since the leads may be provided as part of the tube 14 during the tube's manufacturing process), and through the electrode through-bores, as applicable.
- the leads are subsequently electrically connected to the respective electrodes.
- the proximate electrode 16a is inserted in the end of the tube 14, one of the short lengths of tubing is affixed to the proximate electrode 16a, and so on. Adhesive may be used to hold the components together in this manner.
- the plastic or epoxy fill 28 is injected into the space between the tubing portions, electrodes, and partially into the tube 14, and is allowed to set. The end of the fill 28 is rounded, as shown in FIG.
- the catheter 12a can be manufactured according to a number of different methods and/or steps.
- the catheter could be extruded from a machine.
- the catheter 12a is provided with four electrode.
- the two outer ring electrodes 16a, 16d inject a current into the tissue, and the two inner electrodes 16b, 16c measure the resulting voltage, as shown schematically in FIG. 7 .
- the electrodes 16a-16d are respectively connected to the leads 18a-18d that provide an electrical connection to the other end of the catheter along the wall of the tubing or in the lumen.
- the reads 18a-18d end in an electrical multi-channel connector 34 that can be plugged into the impedance spectrometer 20.
- FIG. 3 shows a second, alternative embodiment of the catheter 12b.
- the catheter i2b has four tubular or ring-like electrodes 36a-36d simply placed over (and adhered to) the exterior surface of the tubing 14, with the leads extending from the electrodes down through the tube wall.
- the electrodes would have to be as thin as possible to minimize surface roughness.
- FIGS. 4A-4C show a third embodiment of the catheter 12c.
- the catheter 12c is generally similar to the catheter 12a, but has spacers 42, provided with annular internal lips, into which flanged electrodes 44 lock into place. More specifically, each flanged electrode 44 has a cylindrical central portion 46 having a first diameter and an annular side surface, two extensions 48 attached to the ends of the central portion and coaxial therewith, and an axial through-bore.
- the extensions 4B each have a second, reduced diameter, but instead of being purely cylindrical, the extensions 48 have annular lips 50 that face towards the peripheral portion 46.
- the spacers 42 which are made of flexible plastic tubing or the like, each have two annular, inwardly-facing shoulders 52 spaced back a bit from the open ends of the spacers 42.
- the electrode extensions 48 are dimensioned to fit within the spacers 42, such that the lips 50 abut the shoulders 52, locking the Ranged electrodes 44 to the spacers 42.
- the catheter 12c is assembled similarly to the catheter 12a, as described above. More specifically, the leads 18a-18d are electrically connected to the electrodes 44 and are threaded through the spacers and electrodes, and the electrodes 44 are locked into successive spacers 42 to form an assembly of four electrodes 44. As should be appreciated, since the electrodes 44 simply snap into the spacers 42, assembly is much quicker. Finally, the assembly is filled with the epoxy or plastic fill 28 to further hold the assembly together and to provide a rounded tip, e.g ., as shown in FIG. 2A . Also, the ends of the leads 18a-18d are connected to the multi-channel connector 34.
- the diameter of the central portions 46 of the electrodes 44 may be initially slightly greater than the outer diameters of the spacers 42, as shown in FIG. 4C . Then, once the catheter 12c is assembled, the outer surface of the catheter is sanded, removing the portions 54 of the electrodes 44 that extend past the spacers 42.
- FIGS. 5A-5C show a fourth embodiment of the catheter 12d.
- the catheter 12d comprises: an injection-molded, plastic tip 60; four electrodes 62a-62d; one or three spacers 64a-64c three spacers are needed for a four electrode catheter): dual-lumen tubing 66 or the like; and the cables or leads 18a-18d.
- the plastic tip 60 comprises a rounded fore portion 68 and a rounded, trough-like projection 70 that extends back from the fore portion 68.
- the tip 60 can be injection molded, or it can be made via another suitable manufacturing process.
- the electrodes 62a-62d and spacers 64a-64c are generally similar in shape.
- Each has a small, cylindrical passageway 72 for the cables 18a-18d, as well as a rounded through-bore 74 through which the trough-like projection 70 of the tip 60 is dimensioned to fit ( i.e., the rounded through-bores 74 and projection 70 are complementary in shape).
- the outer diameters of the electrodes and spacers are the same as the outer diameter of the tip 60, which has the same outer diameter as the tubing 66.
- the cables 18a-18d are inserted through the passageways 72, as applicable. Then, the portion of the projection 70 not covered by electrodes and spacers is slid into the tubing 66, as shown in FIG. 5A .
- Appropriate fastening means such as a solvent or an adhesive, are used to hold the components of the catheter 12d together.
- the rounded through-bores 74 and projection 70 can be provided in any of a number of complementary shapes.
- the projection and through-bores can be V-shaped, square, or circular, However, having a V-or trough-shaped projection, or a projection with another shape where the electrodes and spacers have to be oriented in a particular manner to be positioned over the projection, facilitates assembly and enhances structural stability.
- the system 10 generally consists or three elements: any of the catheters 12a-12d; the impedance spectrometer 20; and the signal processing device 22.
- the impedance spectrometer 20 is an electronic instrument that includes electrical patient isolation and can measure the impedance spectrum of the mucosa in the range of 10 Hz (or thereabouts) to 10 MHz (or thereabouts).
- the spectrum may be obtained by a frequency sweep from a synthesizer or by a pulse, and processed by such methods as synchronous demodulation or Fast Fourier Transform, or any other similar method.
- the output of the spectrometer 20 is the complex impedance spectrum measured in digital form.
- Spectrometers and processing methods suitable for adaptation for use in the present invention are well known to those of skill in the art, for example, as shown in U.S. Pat. No. 5,807,272 to Kun et al. , U.S. Pat. No. 5,633,801 to Bottman , and U.S. Pat. No. 5,454,377 to Dzwonczyk et al .
- the signal processing device 22 may be an appropriately-programmed general purpose computer, or a dedicated analog and/or digital device, both of which are well known to those of ordinary skill in the art.
- the signal processing device 22 may graph or plot the spectrum for visual analysis, as discussed in further detail below.
- the signal processing device 22 may utilize a pattern recognition algorithm or system (e.g ., running as software) or the like for analyzing the complex impedance spectrum itself.
- the pattern recognition system uses a previously trained or calibrated algorithm to classify the impedance spectrum measured and provided by the spectrometer 20.
- the output of this system is a numerical score (or other reference point) in an ischemic damage index scale 80 validated experimentally via MRI's, chemical analysis, biopsy samples, or the like.
- the signal processing device 22, implementing the pattern recognition system analyzes the impedance spectrum to determine to what extent the impedance spectrum of the analyzed tissue deviates from that of normal tissue.
- the degree and character of deviation provides an actual measure of tissue damage, which translates into the ischemic damage index scale 80, as validated experimentally ( e.g ., heavily damaged tissue, as determined experimentally, will have a certain pattern, and slightly damaged tissue, as also determined experimentally, will have a different pattern).
- this shape is the arc of a circle when plotted in the complex plane.
- the spectra of the damaged tissue loses this characteristic shape.
- the spectra of the damaged tissue become sigmoid- or S-shaped, deviating significantly from the normal tissue spectra.
- FIGS. 8A-11C show averaged experimental data obtained in the small intestine of a group of test subjects subjected to a period of intestinal ischemia followed by a period of reperfusion (restored blood flow), in comparison to a group of test subjects in which normal perfusion and oxygenation was maintained.
- the data is presented in both the frequency plots and in the complex plane.
- the Nyquist plots (comp)ex plane) the data has been normalized so that the shapes of the curves can be more easily compared, e.g ., the point at the highest measurement frequency (300 KHz) has an adimensional impedance of 1 and a phase angle of 0.
- FIGS. 8A-8C show the impedance spectra of intestine with less than ten minutes of reduced blood flow, wherein the intestine is already ischemic, with associated rising acidity.
- FIGS. 8A and 8B show the average amplitude and phase impedance spectra, respectively, of both normal intestine and the intestine subjected to reduced blood flow
- FIG. 8C shows the normalized Nyquist plot of the normal and ischemic intestinal tissue.
- the tissue is not yet damaged, and the spectra are not easily distinguishable from the spectra of the normally perfused intestines. Note that the spectra contain some noise, but resemble the circular arc predicted by the Cole-Cole model.
- FIGS. 9A and 9B show the average amplitude and phase impedance spectra, respectively, of both normal intestine and intestine after 1.5 hours of severe ischemia
- FIG. 9C shows the normalized Nyquist plot of the normal and ischemic intestinal tissue.
- the ischemic tissue has suffered moderate damage, and the spectra have become clearly distinguishable
- the ischemic tissue spectra have lost their circular shape and have taken on a sigmoidal shape with several inflection points.
- FIGS. 10A-10C show similar plots for normal intestines and intestines after two hours of severe ischemia. By now, the damage is even more severe, and the spectra have become even more distorted.
- FIGS. 11A-11C show the spectra of normal intestines and intestines after an hour of ischemia followed by 1.5 hours ofreperfusion. After an hour of ischemia, the tissue has suffered some damage. However, after being reperfused, most of this damage has been reversed, and the spectra of the damaged tissue have largely regained their characteristic shape, although they are still somewhat abnormal and are still moderately distinguishable from the spectra of the normal tissue.
- a plot or graph of the complex impedance spectrum of potentially damaged tissue versus the spectrum of normal tissue can be used by appropriately-trained personnel to determine the level of damage due to ischemia, by way of a visual comparison.
- the signal processing device 22 may be configured to graph or plot the spectrum for visual analysis, accordingly the general guidelines given above, on a screen or monitor, or by way of a print-out.
- the signal processing device 22 can be configured to automatically determine tissue damage, by way of the pattern recognition system or other standard signal processing techniques, such as filtering, or smoothing and extracting inflection points by analysis of derivatives.
- Another alternative is the use of principal component decomposition or any other method of extracting a characteristic vector describing the shape of the spectrum. Such a characteristic vector can then be analyzed by a classifying or pattern recognition algorithm to provide a score in a predetermined tissue damage scale.
- a classifying or pattern recognition algorithm can use one of many standard techniques for classification and/or pattern recognition, such as Bayesian statistics, neural networks, fuzzy logic, statistical classifiers, expert systems, or any combination of these. Further detail regarding a pattern recognition system suitable for use or adaptation for use in the present invention can be found in U.S. Pat. No. 5,807,272 to Kun et al. ,
- catheters of the present invention have been illustrated as having Ag/AgCl electrodes, one of ordinary skill in the art will appreciate that other type of electrodes could be used instead without departing from the scope of the invention.
- the electrodes and spacers of the fourth embodiment of the catheter have been illustrated as having separate passageways and through-bores, one of ordinary skill in the art will appreciate that the passageways and through-bores could be connected, i.e., they do not have to be separate openings, as long as there is a space for the leads.
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Abstract
Description
- The present invention relates to systems for monitoring and quantifying ischemic damage in tissues.
- The gastrointestinal mucosa is at great risk of ischemia in the critically ill, and its disruption has been shown to he the motor of multiple organ failure, a leading cause of death. Knowledge of the level of damage can help guide therapy, reversing moderate damage and/or preventing further complications. For example, as indicated by path A in
FIG. 6 , the status of a healthy person's mucosa changes little, if at all, over time. Path C shows how the damage level of an ill person's ischemic mucosa greatly increases over the course of several hours if unchecked. However, as shown by path B, further damage can be arrested if the ischemic damage is detected and an appropriate course of treatment is undertaken. Unfortunately, there exists no clinically suitable method to directly monitor is chemic mucosal damage in the gastrointestinal tract of the critically ill patient. - Impedance spectroscopy has been used to detect ischemia (a condition of inadequate blood flow and oxygen delivery to a given tissue) in biological tissues using different instrumental methods. Impedance spectroscopy differs from other impedance measurements (which have long been used for a variety of biomedical applications such as cardiac output estimation, body fat measurement, and plethismography) in that it involves multiple measurements over a range of frequencies that as a whole contain significantly more information of the structural and electrical properties of the sample. For example,
U.S. Pat. No. 5,434,377 to Dzwoczyk et al . teaches the assessment of ischemia in the myocardium,U.S. Pat. No. 5,807,272 to Kun el al. teaches the assessment of ischemia in directly accessible tissues (surface or subjacent tissue), andU.S. Pat. No. 6,055,452 to Pearlman shows the general characterization of the status and properties of tissues. However, none of these references show or describe a clinically acceptable method for impedance spectroscopy measurements of the inner wall of hollow viscous organs such as the gastrointestinal mucosa, in vivo or in situ. - On the other hand, several other methods have been devised to detect and/or monitor gastrointestinal ischemia using different measurement technologies. These include tonometry (as shown in
U.S. Pat. Nos. 5,788,631 and6,010,453 to Fiddian-Green ), direct in situ measurement using an electrochemical sensor (as shown inU.S. Pat. No. 5,158,083 to Sacristán ), and direct in situ measurement using an optochemical sensor (as shown inU.S. Pat. No. 5,423,320 to Salzman et al. ) Additionally,U.S. Pat. No. 5,771,894 to Richards et al . shows external, non-invasive measurement using a magnetometer. - Numerous gastrointestinal catheter combinations, using electrodes or other sensors, have been used over the years for various measurements and medical applications. For example,
U.S. Pat. No. 5,657,759 to Essen-Moller discloses a gastrointestinal output catheter,U.S. Pat. Nos. 5,848,965 and5,438,985, both to Essen-Moller , show a gastric pH sensor/catheter combination, andU.S. Pat. No. 5,477,854 to Essen-Moller discloses a helicobater pylori gastric infection sensor. Furthermore,U.S. Pat. No. 5,833,625 to Essen-Moller shows a gastric reflux monitor,U.S. Pat. No. 6,010,453 to Fiddian-Green shows a pressure nasogastric sump and tonometer combination,U.S. Pat. No. 5,158,083 to Sacristán et al . discloses a miniature pCO2 probe and catheter, andU.S. Pat. No. 5,423,320 to Salzman et al . shows an air tonometry sensor and catheter. - Several therapies have been proposed to limit or reverse the gastrointestinal mucosal damage and/or the associated complications in critical patients, including, for example, aggressive hemodynamic resuscitation (as shown in Gutierrez et al.), NO synthase modulators (as shown in
U.S. Pat. No. 5,585,402 to Moncada et al .), rBPI protein (as shown inU.S. Pat. No. 6,017,881 to Ammos et al .), oral glutamine (as shown inU.S. Pat. No. 5,981,590 to Panigrahi et al .), and DHEA (as shown inU.S. Pat. No. 5,922,701 to Araneo ). All of these can be optimally effective if they are administered within ideal treatment time windows depending on the status of the mucosa. - Document
US-A-4 729 385 system for monitoring mucosal damage in hollow viscous organs comprising two probes electrically connected to an impedance spectrometer and a signal processing device configured to process the detected impedance spectrum for a determination of the extent to which the mucosa is damaged. - Both probes carry two electrodes. During use the first probe located within an epithelial cavity of a subject electrically interacts with the second probe positioned in a blood vessel to measure the impedance of the tissues lying between the two probes.
- Accordingly, it is a primary object of the present invention to provide an impedance spectroscopy system, not only for detecting ischemia, but also for monitoring and quantifying ischemic mucosal damage, that is of great clinical value as a therapeutic guide for patients with intestinal ischemia and/or shock.
- Another primary object of the present invention is to provide an impedance spectroscopy system and catheter for the continuous monitoring of the level of damage, of the gastric mucosa in critically ill patients.
- The invention is defined in the
independent claim 1. Preferred embodiments are defined in the dependent claims. The claimed impedance spectroscopy system for monitoring ischemic mucosal damage in hollow viscous organs comprises a sensor catheter and an impedance spectrometer far electrically driving the catheter to obtain 8 complex impedance spectrum of tissue proximate the catheter. According to the present invention, the complex impedance spectrum is used to determine the extent to which the tissue is damaged, as opposed to determining if the tissue is ischemic. More specifically, as mentioned above, ischemia is a condition of inadequate blood flow and oxygen delivery to a given tissue, which may or may not result in tissue, damage (i.e, is chemic tissue can be undamaged, and vice versa). Thus, detecting tissue ischemia does not result in a measurement of tissue damage, and a different process, as implemented in the present invention, must be utilized to do so. - The catheter, which is configured to be inserted into any hollow viscous organ, comprises four Ag/AgCl electrodes positioned on an end tip of the catheter. The electrodes are functionally ring-shaped, and are coaxially spaced apart a short distance from one another. The outer two ring electrodes inject current into the tissue, and the inner two electrodes measure the resulting voltage. Leads, electrically connected to the electrodes, extend along the wall of the catheter tubing or in a lumen portion of the tubing, and terminate at an interface plug suitable for connection to the impedance spectrometer. Once the catheter is in place in one of a patient's hollow viscous organs, the impedance spectrometer causes the electrodes in the tip of the catheter to inject a current into the mucosal tissue at different frequencies, allowing for the measurement of the tissue's complex impedance spectrum. The spectrum contains information of the structural and metabolic status of the tissue, and can be used to quantify the level of damage. More specifically, the spectrum can be appropriately graphically plotted against the spectrum of normal tissue, allowing for a direct visual comparison by trained personnel, and, therefore, an indication or measurement of damage. Alternatively, a standard pattern recognition system or the like may be used to automatically analyze the complex impedance spectrum and quantify the severity of the mucosal injury.
- These and other features, aspects, and advantages of the present invention will become better understood with respect to the following description, appended claims, and accompanying drawings, in which:
-
FIG. 1 is a schematic view of an impedance spectroscopy system for monitoring ischemic mucosal damage in hollow viscous organs; -
FIG. 2A is a cross-sectional elevation view of a catheter for use with the impedance spectroscopy system; -
FIG. 2B is a perspective view of an electrode portion of the catheter; -
FIG. 2C is a cross-sectional plan view of an alternative upper portion of the catheter; -
FIG. 3 is a cross-sectional elevation view of a second embodiment of the catheter; -
FIG. 4A is an exploded view of a third embodiment of the catheter; -
FIG. 4B is an elevation view, partly in cross-section, of a portion of the catheter shown inFIG. 4A , once assembled; -
FIG. 4C is a detail view of a portion ofFIG. 4A ; -
FIGS. 5A-5C are perspective views of a fourth embodiment of the catheter; -
FIG. 6 is a diagrammatic graph showing mucosal structure (e.g., as lining an intestinal wall) and different courses of mucosal ischemic pathogenesis; -
FIG. 7 is a schematic illustration of the operation of the catheter; and -
FIGS. 8A-11C are various graphs or plots illustrating how ischemic mucosal damage in hollow viscous organs is detected and/or quantified according to the present invention. - Turning now to
FIGS. 1-11C , preferred embodiments of animpedance spectroscopy system 10 andcatheters 12a-12d for ischemic mucosal damage monitoring in hollow viscous organs, according to the present invention, will now be given. Thecatheters 12a-12d are generally similar, in that each one has four electrodes with annular side surfaces positioned at a distal end of the catheter. For example, thecatheter 12a comprises aflexible tube 14 and four generally cylindrical electrodes 16a-16d disposed at one end thereof. The electrodes 15a-16d are electrically connected, via leads 18a-18d extending up through thetube 14, to animpedance spectrometer 20 portion of thesystem 10. Thespectrometer 20 is used in conjunction with asignal processing device 22, such as an appropriately-programmed general purpose computer, for processing the complex impedance spectrum to detect tissue damage. To monitor mucosal damage, the catheter is placed in one of a patient's hollow viscous organs 35, and current is injected by two of theelectrodes 16a, 16d at a range of frequencies. The other twoelectrodes spectrometer 20 andsignal processing device 22. -
FIGS. 2A-2C show a first embodiment of thecatheter 12a. Thecatheter 12a comprises the flexibleplastic tube 14 that can be inserted in any hollow viscous organ. At the distal end or tip of thetube 14 are located the four electrodes 16a-16d that function as ionic-current-to-electronir-current transducers, such as Ag/AgCl electrodes. The electrodes are substantially identical. As shown inFIG. 2B , each has a cylindricalcentral portion 24 having a first diameter and an annular side surface, and twocylindrical extensions 26 attached to the ends of the central portion and coaxial therewith. Theextensions 26 have a second, reduced diameter, and each electrode 16a-16d has an axial through-bore. - The electrodes 16a-16d are spaced equally apart from one another along the distal tip of the
catheter 12a, and are separated by spacers (short lengths of tubing) 27a-27d. As best seen inFIG. 2A , the annular side walls of thecentral portions 24 of the electrodes 16a-16d are the only portions thereof that are exposed to the outside of thecatheter 12a. Thus, each electrode 16a-16d is ring-like in functionality, and the distal end of the catheter (with the electrodes) is generally radially symmetric. The catheter, therefore, will provide the same measurements regardless of its radial orientation in an organ. - The diameters of the
central electrode portions 24 are about the same as the outer diameter of thetube 14. This ensures that the outer surface of thecatheter 12a is relatively smooth, e.g., that it has no more than minor surface roughness or undulations. The electrodes 16a-16d are respectively electrically connected to theleads 18a-18d (via soldering, welding, or the like) in the electrodes' axial through-bores. The leads from the distal threeelectrodes 16b-16d extend through the axial through-bores of the other electrodes, as applicable. The electrodes 16a-16d, leads 18a-18d, and short portions of tubing are kept in place and stabilized via an epoxy orplastic fill 28. - The
catheter 12a may be a stand alone sensor catheter, or it may be provided as part of a feeding/sump tube or some other type of life support tube or catheter. For example, as shown inFIG. 2A , thecatheter 12a doubles as a feeding tube. More specifically, the end of thecatheter 12a is provided with the electrodes 16a-16d, while the remainder of thetube 14 is left hollow to act as afeeding line 29. Additionally, thecatheter tube 14 may include a second lumen for sampling and feeding, like a Levin type gastric catheter, and/or a third lumen for a vented feeding/sump tube, as in a Salem type gastric catheter. For example, as shown inFIG. 2C , theelectrical leads 18a-18d extend drown through a side wall portion of thetube 14 having avent lumen 30 and a feeding/sump lumen 32. - To manufacture the
catheter 12a, theleads 18a-18d are fed through thetube 14, if needed (since the leads may be provided as part of thetube 14 during the tube's manufacturing process), and through the electrode through-bores, as applicable. The leads are subsequently electrically connected to the respective electrodes. Then, the proximate electrode 16a is inserted in the end of thetube 14, one of the short lengths of tubing is affixed to the proximate electrode 16a, and so on. Adhesive may be used to hold the components together in this manner. Finally, the plastic or epoxy fill 28 is injected into the space between the tubing portions, electrodes, and partially into thetube 14, and is allowed to set. The end of thefill 28 is rounded, as shown inFIG. 2A , to ease insertion of the catheter into a patient. As will be appreciated by those of skill in the manufacturing arts, thecatheter 12a can be manufactured according to a number of different methods and/or steps. For example, the catheter could be extruded from a machine. - The
catheter 12a is provided with four electrode. The twoouter ring electrodes 16a, 16d inject a current into the tissue, and the twoinner electrodes FIG. 7 . As mentioned above, the electrodes 16a-16d are respectively connected to theleads 18a-18d that provide an electrical connection to the other end of the catheter along the wall of the tubing or in the lumen. At the other, proximal end of the catheter, thereads 18a-18d end in an electricalmulti-channel connector 34 that can be plugged into theimpedance spectrometer 20. -
FIG. 3 shows a second, alternative embodiment of the catheter 12b. Here, the catheter i2b has four tubular or ring-like electrodes 36a-36d simply placed over (and adhered to) the exterior surface of thetubing 14, with the leads extending from the electrodes down through the tube wall. In this case, the electrodes would have to be as thin as possible to minimize surface roughness. -
FIGS. 4A-4C show a third embodiment of the catheter 12c. The catheter 12c is generally similar to thecatheter 12a, but has spacers 42, provided with annular internal lips, into whichflanged electrodes 44 lock into place. More specifically, eachflanged electrode 44 has a cylindricalcentral portion 46 having a first diameter and an annular side surface, twoextensions 48 attached to the ends of the central portion and coaxial therewith, and an axial through-bore. The extensions 4B each have a second, reduced diameter, but instead of being purely cylindrical, theextensions 48 haveannular lips 50 that face towards thecentrale portion 46. Additionally, thespacers 42, which are made of flexible plastic tubing or the like, each have two annular, inwardly-facingshoulders 52 spaced back a bit from the open ends of thespacers 42. As shown inFIG. 4B , theelectrode extensions 48 are dimensioned to fit within thespacers 42, such that thelips 50 abut theshoulders 52, locking the Rangedelectrodes 44 to thespacers 42. - The catheter 12c is assembled similarly to the
catheter 12a, as described above. More specifically, theleads 18a-18d are electrically connected to theelectrodes 44 and are threaded through the spacers and electrodes, and theelectrodes 44 are locked intosuccessive spacers 42 to form an assembly of fourelectrodes 44. As should be appreciated, since theelectrodes 44 simply snap into thespacers 42, assembly is much quicker. Finally, the assembly is filled with the epoxy orplastic fill 28 to further hold the assembly together and to provide a rounded tip, e.g., as shown inFIG. 2A . Also, the ends of theleads 18a-18d are connected to themulti-channel connector 34. - To give the catheter 12c a smooth, low-friction outer surface, the diameter of the
central portions 46 of theelectrodes 44 may be initially slightly greater than the outer diameters of thespacers 42, as shown inFIG. 4C . Then, once the catheter 12c is assembled, the outer surface of the catheter is sanded, removing theportions 54 of theelectrodes 44 that extend past thespacers 42. -
FIGS. 5A-5C show a fourth embodiment of thecatheter 12d. Thecatheter 12d comprises: an injection-molded,plastic tip 60; fourelectrodes 62a-62d; one or threespacers 64a-64c three spacers are needed for a four electrode catheter): dual-lumen tubing 66 or the like; and the cables or leads 18a-18d. As best shown inFIG. 5B , theplastic tip 60 comprises arounded fore portion 68 and a rounded, trough-like projection 70 that extends back from thefore portion 68. As indicated, thetip 60 can be injection molded, or it can be made via another suitable manufacturing process. Theelectrodes 62a-62d andspacers 64a-64c are generally similar in shape. Each has a small,cylindrical passageway 72 for thecables 18a-18d, as well as a rounded through-bore 74 through which the trough-like projection 70 of thetip 60 is dimensioned to fit (i.e., the rounded through-bores 74 andprojection 70 are complementary in shape). Additionally, the outer diameters of the electrodes and spacers are the same as the outer diameter of thetip 60, which has the same outer diameter as thetubing 66, To assemble thecatheter 12d, thecables 18a-18d are respectively electrically connected to theelectrodes 62a-62d, and alternatingelectrodes 62a-62d andspacers 64a-64c are slid over theprojection 70. Simultaneously, thecables 18a-18d are inserted through thepassageways 72, as applicable. Then, the portion of theprojection 70 not covered by electrodes and spacers is slid into thetubing 66, as shown inFIG. 5A . Appropriate fastening means, such as a solvent or an adhesive, are used to hold the components of thecatheter 12d together. - As should be appreciated, the rounded through-
bores 74 andprojection 70 can be provided in any of a number of complementary shapes. For example, the projection and through-bores can be V-shaped, square, or circular, However, having a V-or trough-shaped projection, or a projection with another shape where the electrodes and spacers have to be oriented in a particular manner to be positioned over the projection, facilitates assembly and enhances structural stability. - referring back to
FIG. 1 , thesystem 10 generally consists or three elements: any of thecatheters 12a-12d; theimpedance spectrometer 20; and thesignal processing device 22. Theimpedance spectrometer 20 is an electronic instrument that includes electrical patient isolation and can measure the impedance spectrum of the mucosa in the range of 10 Hz (or thereabouts) to 10 MHz (or thereabouts). The spectrum may be obtained by a frequency sweep from a synthesizer or by a pulse, and processed by such methods as synchronous demodulation or Fast Fourier Transform, or any other similar method. The output of thespectrometer 20 is the complex impedance spectrum measured in digital form. Spectrometers and processing methods suitable for adaptation for use in the present invention are well known to those of skill in the art, for example, as shown inU.S. Pat. No. 5,807,272 to Kun et al. ,U.S. Pat. No. 5,633,801 to Bottman , andU.S. Pat. No. 5,454,377 to Dzwonczyk et al . - Once the complex impedance spectrum is obtained, the results are processed by the
signal processing device 22. Thesignal processing device 22 may be an appropriately-programmed general purpose computer, or a dedicated analog and/or digital device, both of which are well known to those of ordinary skill in the art. For processing the complex impedance spectrum obtained by thespectrometer 20, thesignal processing device 22 may graph or plot the spectrum for visual analysis, as discussed in further detail below. Alternatively, thesignal processing device 22 may utilize a pattern recognition algorithm or system (e.g., running as software) or the like for analyzing the complex impedance spectrum itself. The pattern recognition system uses a previously trained or calibrated algorithm to classify the impedance spectrum measured and provided by thespectrometer 20. The output of this system is a numerical score (or other reference point) in an ischemicdamage index scale 80 validated experimentally via MRI's, chemical analysis, biopsy samples, or the like. In other words, thesignal processing device 22, implementing the pattern recognition system, analyzes the impedance spectrum to determine to what extent the impedance spectrum of the analyzed tissue deviates from that of normal tissue. The degree and character of deviation provides an actual measure of tissue damage, which translates into the ischemicdamage index scale 80, as validated experimentally (e.g., heavily damaged tissue, as determined experimentally, will have a certain pattern, and slightly damaged tissue, as also determined experimentally, will have a different pattern). - More specifically, as discussed above, the impedance spectrum of the analyzed tissue is obtained by making multiple complex impedance measurements at different frequencies over the range of interest. At each frequency, an amplitude, Z, and a phase,φ, of the tissue response are obtained. These values are then plotted as a function of frequency, or combined and plotted in the complex plane (resistance vs. reactance) in a Nyquist or a Cole-Cole plot (this latter term applies specifically to tissue impedance spectra plots), where resistance (R) and reactance (X) are defined as:
Analysis of these plots shows that normal tissue spectra have a characteristic shape or pattern. According to the Cole-Cole electric model of biological tissues, this shape is the arc of a circle when plotted in the complex plane. However, if tissue is damaged after an extended period of ischemia, the spectra of the damaged tissue loses this characteristic shape. In fact, when plotted in the complex plane, the spectra of the damaged tissue become sigmoid- or S-shaped, deviating significantly from the normal tissue spectra. -
FIGS. 8A-11C show averaged experimental data obtained in the small intestine of a group of test subjects subjected to a period of intestinal ischemia followed by a period of reperfusion (restored blood flow), in comparison to a group of test subjects in which normal perfusion and oxygenation was maintained. The data is presented in both the frequency plots and in the complex plane. For the Nyquist plots (comp)ex plane), the data has been normalized so that the shapes of the curves can be more easily compared, e.g., the point at the highest measurement frequency (300 KHz) has an adimensional impedance of 1 and a phase angle of 0. -
FIGS. 8A-8C show the impedance spectra of intestine with less than ten minutes of reduced blood flow, wherein the intestine is already ischemic, with associated rising acidity. In particular,FIGS. 8A and 8B show the average amplitude and phase impedance spectra, respectively, of both normal intestine and the intestine subjected to reduced blood flow, whileFIG. 8C shows the normalized Nyquist plot of the normal and ischemic intestinal tissue. As can be seen, although the intestine with reduced blood flow is ischemic, the tissue is not yet damaged, and the spectra are not easily distinguishable from the spectra of the normally perfused intestines. Note that the spectra contain some noise, but resemble the circular arc predicted by the Cole-Cole model. -
FIGS. 9A and9B show the average amplitude and phase impedance spectra, respectively, of both normal intestine and intestine after 1.5 hours of severe ischemia, whileFIG. 9C shows the normalized Nyquist plot of the normal and ischemic intestinal tissue. Here, the ischemic tissue has suffered moderate damage, and the spectra have become clearly distinguishable B the ischemic tissue spectra have lost their circular shape and have taken on a sigmoidal shape with several inflection points. -
FIGS. 10A-10C show similar plots for normal intestines and intestines after two hours of severe ischemia. By now, the damage is even more severe, and the spectra have become even more distorted. -
FIGS. 11A-11C show the spectra of normal intestines and intestines after an hour of ischemia followed by 1.5 hours ofreperfusion. After an hour of ischemia, the tissue has suffered some damage. However, after being reperfused, most of this damage has been reversed, and the spectra of the damaged tissue have largely regained their characteristic shape, although they are still somewhat abnormal and are still moderately distinguishable from the spectra of the normal tissue. - As should be appreciated, a plot or graph of the complex impedance spectrum of potentially damaged tissue versus the spectrum of normal tissue, e.g., as shown in
FIGS. 8A-11C , can be used by appropriately-trained personnel to determine the level of damage due to ischemia, by way of a visual comparison. Accordingly, thesignal processing device 22 may be configured to graph or plot the spectrum for visual analysis, accordingly the general guidelines given above, on a screen or monitor, or by way of a print-out. - Alternatively, the
signal processing device 22 can be configured to automatically determine tissue damage, by way of the pattern recognition system or other standard signal processing techniques, such as filtering, or smoothing and extracting inflection points by analysis of derivatives. Another alternative is the use of principal component decomposition or any other method of extracting a characteristic vector describing the shape of the spectrum. Such a characteristic vector can then be analyzed by a classifying or pattern recognition algorithm to provide a score in a predetermined tissue damage scale. Such an algorithm can use one of many standard techniques for classification and/or pattern recognition, such as Bayesian statistics, neural networks, fuzzy logic, statistical classifiers, expert systems, or any combination of these. Further detail regarding a pattern recognition system suitable for use or adaptation for use in the present invention can be found inU.S. Pat. No. 5,807,272 to Kun et al. , - Although the catheters of the present invention have been illustrated as having Ag/AgCl electrodes, one of ordinary skill in the art will appreciate that other type of electrodes could be used instead without departing from the scope of the invention.
- Although the electrodes and spacers of the fourth embodiment of the catheter have been illustrated as having separate passageways and through-bores, one of ordinary skill in the art will appreciate that the passageways and through-bores could be connected, i.e., they do not have to be separate openings, as long as there is a space for the leads.
- Since certain changes may be made in the above described impedance spectroscopy system and catheter for ischemic mucosal damage monitoring in hollow viscous organs, it is intended that all of the subject matter of the above description or shown in the accompanying drawings shall be interpreted merely as examples illustrating the inventive concept herein and shall not be construed as limiting the invention.
Claims (9)
- A system (10) for monitoring mucosal damage in hollow viscous organs comprising:(a) a catheter (12a; 12b; 12c; 12d) suitable for insertion into a hollow viscous organ (25) and having four spaced apart annular electrodes (16a-16d; 36a-36d; 44; 62a-62d) positioned proximate a first end of the catheter (12a; 12b; 12c; 12d), said electrodes being respectively electrically connected to a plurality of electrical leads (18a-18d) extending through the catheter from the electrodes towards a second end of the catheter and terminating at a connector (34);(b) an impedance spectrometer (20) electrically connected to the electrodes (16a-16d; 36a-36d; 44; 62a-62d) in the catheter by way of the connector (34), said impedance spectrometer being configured to electrically drive the electrodes once the catheter is inserted into the hollow viscous organ (25) by injecting currents by the outer two electrodes of the catheter, and to use the inner two electrodes from the same catheter to measure the resulting voltage to obtain a complex impedance spectrum of mucosa lining the hollow viscous organ; and(c) a signal processing device (22) connected to the impedance spectrometer (20) and configured to process the complex impedance spectrum for a determination of the extent to which the mucosa is damaged.
- The system of Claim 1 wherein the signal processing device (22) is further configured to generate a reference point on an experimentally-validated damage index scale, as a measure of the extent to which the mucosa is damaged, based upon the processed complex impedance spectrum.
- The system of Claim 1 or 2 wherein the signal processing device (22) is further configured to compare the processed complex impedance spectrum of the mucosa to a complex impedance spectrum of normal tissue, and to utilize the comparison to generate a reference point on an experimentally-validated damage index scale, as a measure of the extent to which the mucosa is damaged.
- The system of Claim 3 wherein the signal processing device (22) is configured to compare, the processed complex impedance spectrum of the mucosa to the complex impedance spectrum of normal tissue by utilizing a pattern recognition algorithm.
- The system of Claim 1 wherein the signal processing device (22) is configured to graphically represent the complex impedance spectrum of the mucosa and a complex impedance spectrum of normal tissue in a format appropriate for a direct visual comparison between the complex impedance spectrum of the mucosa and the complex impedance spectrum of normal tissue, by appropriately trained personnel, for purposes of determining the extent to which the mucosa is damaged.
- The system of any of Claims 1 to 5 wherein:(a) the catheter (12d) further comprises:(i) a tip (60) having a rounded fore portion (68) and a projection (70) extending back from the fore portion;(ii) at least one spacer (64a-64c) having: an annular side surface; space and a through-bore (74) extending through the spacer (64a-64c) complementary in shape to the projection (70), and(iii) a length of tubing (66) suitable for insertion into hollow viscous organs;(b) the electrodes (62a-62d) each have: an annular side surface; and a through-bore (74) extending through the electrode and complementary in shape to the projection;(c) the electrodes (62a-62d) are positioned over the projection (70) with the projection extending through the electrode through-bores (74), said electrodes being spaced apart from one another by the at least one spacer (64a-64c) being positioned there between and over the projection (70) with the projection extending through the spacer through-bore (74); and(d) a rear portion of the projection lies inserted within the tubing (66): with the electrodes and at least one spacer being positioned between the rounded fore portion (68) of the tip (60) and an end of the tubing.
- The System of any of Claims 1 to 5 wherein:(a) the catheter further comprises a length of tubing suitable for insertion into hollow viscous organs;(b) the electrodes (44) each comprise: a cylindrical central portion (46) having an annular side wall and a diameter generally equal to an outer diameter of the tubing; first and second cylindrical extensions (48) attached to a top and a bottom of the cylindrical central portion (46), respectively, and coaxial therewith, said first and second cylindrical extensions having a diameter smaller than the diameter of the cylindrical central portion; and an axial bore extending through the cylindrical central portion and first and second cylindrical extensions; and(c) the electrodes (44) are spaced apart from one another by annular spacers (42) positioned over the cylindrical extensions and abutting the cylindrical central portions (46).
- The system of Claim 7 wherein:(a) the spacers each have two annular, inwardly-facing shoulders (52) paced back from the ends of the spacers; and(b) the cylindrical extensions of the electrodes each have an annular lip (50) facing towards the cylindrical central portions, wherein the cylindrical extensions are dimensioned to fit within the spacers such that the lips (50) abut the shoulders (52), locking the electrodes to the spacers.
- The system of claim 6 wherein the spacers are three spacers.
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US21928100P | 2000-07-19 | 2000-07-19 | |
EP01116731A EP1174080B1 (en) | 2000-07-19 | 2001-07-18 | Catheter for use in a system for monitoring mucosal damage in hollow viscous organs |
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EP01116731.9 Division | 2001-07-18 | ||
EP01116731A Division EP1174080B1 (en) | 2000-07-19 | 2001-07-18 | Catheter for use in a system for monitoring mucosal damage in hollow viscous organs |
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EP1707116B1 true EP1707116B1 (en) | 2012-06-06 |
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EP08169034A Expired - Lifetime EP2027816B1 (en) | 2000-07-19 | 2001-07-18 | Catheter for ischemic mucosal damage monitoring in hollow viscous organs |
EP01116731A Expired - Lifetime EP1174080B1 (en) | 2000-07-19 | 2001-07-18 | Catheter for use in a system for monitoring mucosal damage in hollow viscous organs |
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EP01116731A Expired - Lifetime EP1174080B1 (en) | 2000-07-19 | 2001-07-18 | Catheter for use in a system for monitoring mucosal damage in hollow viscous organs |
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Families Citing this family (81)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6882879B2 (en) * | 2000-07-19 | 2005-04-19 | Innovamedica S.A. De C.V. | Impedance spectroscopy system and catheter for ischemic mucosal damage monitoring in hollow viscous organs |
GB0219068D0 (en) * | 2002-08-16 | 2002-09-25 | Grampian Univ Hospitals | Apparatus and method |
US7062310B2 (en) | 2003-10-06 | 2006-06-13 | Tyco Electronics Corporation | Catheter tip electrode assembly and method for fabricating same |
US7054690B2 (en) * | 2003-10-22 | 2006-05-30 | Intrapace, Inc. | Gastrointestinal stimulation device |
US20090018507A1 (en) * | 2007-07-09 | 2009-01-15 | Baxano, Inc. | Spinal access system and method |
US8048080B2 (en) | 2004-10-15 | 2011-11-01 | Baxano, Inc. | Flexible tissue rasp |
US9247952B2 (en) | 2004-10-15 | 2016-02-02 | Amendia, Inc. | Devices and methods for tissue access |
US8257356B2 (en) | 2004-10-15 | 2012-09-04 | Baxano, Inc. | Guidewire exchange systems to treat spinal stenosis |
US20080161809A1 (en) * | 2006-10-03 | 2008-07-03 | Baxano, Inc. | Articulating Tissue Cutting Device |
US20110190772A1 (en) | 2004-10-15 | 2011-08-04 | Vahid Saadat | Powered tissue modification devices and methods |
US9101386B2 (en) | 2004-10-15 | 2015-08-11 | Amendia, Inc. | Devices and methods for treating tissue |
US7555343B2 (en) | 2004-10-15 | 2009-06-30 | Baxano, Inc. | Devices and methods for selective surgical removal of tissue |
US8430881B2 (en) | 2004-10-15 | 2013-04-30 | Baxano, Inc. | Mechanical tissue modification devices and methods |
US20060122458A1 (en) * | 2004-10-15 | 2006-06-08 | Baxano, Inc. | Devices and methods for tissue access |
US8062300B2 (en) | 2006-05-04 | 2011-11-22 | Baxano, Inc. | Tissue removal with at least partially flexible devices |
US20100331883A1 (en) * | 2004-10-15 | 2010-12-30 | Schmitz Gregory P | Access and tissue modification systems and methods |
US8221397B2 (en) | 2004-10-15 | 2012-07-17 | Baxano, Inc. | Devices and methods for tissue modification |
US7578819B2 (en) | 2005-05-16 | 2009-08-25 | Baxano, Inc. | Spinal access and neural localization |
US7738969B2 (en) | 2004-10-15 | 2010-06-15 | Baxano, Inc. | Devices and methods for selective surgical removal of tissue |
US8613745B2 (en) | 2004-10-15 | 2013-12-24 | Baxano Surgical, Inc. | Methods, systems and devices for carpal tunnel release |
JP5243034B2 (en) | 2004-10-15 | 2013-07-24 | バクサノ,インク. | Tissue removal device |
US7938830B2 (en) | 2004-10-15 | 2011-05-10 | Baxano, Inc. | Powered tissue modification devices and methods |
US7887538B2 (en) | 2005-10-15 | 2011-02-15 | Baxano, Inc. | Methods and apparatus for tissue modification |
US7857813B2 (en) | 2006-08-29 | 2010-12-28 | Baxano, Inc. | Tissue access guidewire system and method |
US7532933B2 (en) * | 2004-10-20 | 2009-05-12 | Boston Scientific Scimed, Inc. | Leadless cardiac stimulation systems |
US7668667B2 (en) * | 2005-03-07 | 2010-02-23 | Microstrain, Inc. | Miniature stimulating and sensing system |
CN101511292B (en) * | 2005-03-28 | 2011-04-06 | 明诺医学有限公司 | Intraluminal electrical tissue characterization and tuned RF energy for selective treatment of atheroma and other target tissues |
US20080091227A1 (en) * | 2006-08-25 | 2008-04-17 | Baxano, Inc. | Surgical probe and method of making |
US8062298B2 (en) | 2005-10-15 | 2011-11-22 | Baxano, Inc. | Flexible tissue removal devices and methods |
US8092456B2 (en) | 2005-10-15 | 2012-01-10 | Baxano, Inc. | Multiple pathways for spinal nerve root decompression from a single access point |
US20080033465A1 (en) * | 2006-08-01 | 2008-02-07 | Baxano, Inc. | Multi-Wire Tissue Cutter |
US8366712B2 (en) | 2005-10-15 | 2013-02-05 | Baxano, Inc. | Multiple pathways for spinal nerve root decompression from a single access point |
US8403925B2 (en) | 2006-12-06 | 2013-03-26 | St. Jude Medical, Atrial Fibrillation Division, Inc. | System and method for assessing lesions in tissue |
US8449535B2 (en) * | 2005-12-06 | 2013-05-28 | St. Jude Medical, Atrial Fibrillation Division, Inc. | System and method for assessing coupling between an electrode and tissue |
US8998890B2 (en) | 2005-12-06 | 2015-04-07 | St. Jude Medical, Atrial Fibrillation Division, Inc. | Assessment of electrode coupling for tissue ablation |
US9492226B2 (en) | 2005-12-06 | 2016-11-15 | St. Jude Medical, Atrial Fibrillation Division, Inc. | Graphical user interface for real-time RF lesion depth display |
US9254163B2 (en) | 2005-12-06 | 2016-02-09 | St. Jude Medical, Atrial Fibrillation Division, Inc. | Assessment of electrode coupling for tissue ablation |
US8603084B2 (en) * | 2005-12-06 | 2013-12-10 | St. Jude Medical, Atrial Fibrillation Division, Inc. | System and method for assessing the formation of a lesion in tissue |
AU2006321918B2 (en) | 2005-12-06 | 2011-08-25 | St. Jude Medical, Atrial Fibrillation Division Inc. | Assessment of electrode coupling for tissue ablation |
US10362959B2 (en) | 2005-12-06 | 2019-07-30 | St. Jude Medical, Atrial Fibrillation Division, Inc. | System and method for assessing the proximity of an electrode to tissue in a body |
US8406866B2 (en) | 2005-12-06 | 2013-03-26 | St. Jude Medical, Atrial Fibrillation Division, Inc. | System and method for assessing coupling between an electrode and tissue |
WO2007075091A2 (en) * | 2005-12-29 | 2007-07-05 | Rikshospitalet - Radiumhospitalet Hf | Method and apparatus for determining local tissue impedance for positioning of a needle |
EP1892010B1 (en) * | 2006-08-25 | 2010-10-06 | Pulsion Medical Systems AG | Enteral feeding catheter and apparatus for determining the intraabdominal pressure of a patient |
WO2008070867A2 (en) * | 2006-12-07 | 2008-06-12 | Baxano, Inc. | Tissue removal devices and methods |
EP2117639B1 (en) * | 2007-02-21 | 2013-05-22 | St. Jude Medical AB | Detect eating to initiate gastric pacing |
WO2008157513A1 (en) * | 2007-06-15 | 2008-12-24 | Baxano, Inc. | Devices and methods for measuring the space around a nerve root |
US8756806B2 (en) | 2007-06-27 | 2014-06-24 | Flip Technologies Limited | Catheter and a method for producing a catheter |
EP2194861A1 (en) | 2007-09-06 | 2010-06-16 | Baxano, Inc. | Method, system and apparatus for neural localization |
JP5004771B2 (en) * | 2007-11-22 | 2012-08-22 | 株式会社リコー | Image forming apparatus |
US20090137925A1 (en) * | 2007-11-23 | 2009-05-28 | Divya Cantor | Impedance Spectroscopy Cervix Scanning Apparatus and Method |
US8192436B2 (en) | 2007-12-07 | 2012-06-05 | Baxano, Inc. | Tissue modification devices |
US8290578B2 (en) * | 2007-12-28 | 2012-10-16 | St. Jude Medical, Atrial Fibrillation Division, Inc. | Method and apparatus for complex impedance compensation |
US10660690B2 (en) * | 2007-12-28 | 2020-05-26 | St. Jude Medical, Atrial Fibrillation Division, Inc. | System and method for measurement of an impedance using a catheter such as an ablation catheter |
US9204927B2 (en) | 2009-05-13 | 2015-12-08 | St. Jude Medical, Atrial Fibrillation Division, Inc. | System and method for presenting information representative of lesion formation in tissue during an ablation procedure |
JP4452750B2 (en) * | 2008-05-22 | 2010-04-21 | 並木精密宝石株式会社 | Sensor element, sensor system, catheter, and sensor element manufacturing method |
US8206385B2 (en) * | 2008-06-09 | 2012-06-26 | St. Jude Medical, Atrial Fibrillation Division, Inc. | Catheter assembly with front-loaded tip and multi-contact connector |
US8398641B2 (en) | 2008-07-01 | 2013-03-19 | Baxano, Inc. | Tissue modification devices and methods |
US9314253B2 (en) | 2008-07-01 | 2016-04-19 | Amendia, Inc. | Tissue modification devices and methods |
US8409206B2 (en) | 2008-07-01 | 2013-04-02 | Baxano, Inc. | Tissue modification devices and methods |
CA2730732A1 (en) | 2008-07-14 | 2010-01-21 | Baxano, Inc. | Tissue modification devices |
US8386010B2 (en) * | 2008-10-23 | 2013-02-26 | Covidien Lp | Surgical tissue monitoring system |
CZ302036B6 (en) * | 2008-12-08 | 2010-09-15 | Hanzalová@Jitka | Catheter for measuring electrochemical properties of body fluids |
CA2749673A1 (en) | 2009-03-13 | 2010-09-16 | Baxano, Inc. | Flexible neural localization devices and methods |
JP2012520739A (en) * | 2009-03-16 | 2012-09-10 | クリティカル・パフュージョン・インコーポレイテッド | System and method for characteristic parameter evaluation of human stomach impedance spectrum |
US8394102B2 (en) | 2009-06-25 | 2013-03-12 | Baxano, Inc. | Surgical tools for treatment of spinal stenosis |
WO2011072221A1 (en) | 2009-12-11 | 2011-06-16 | St. Jude Medical, Atrial Fibrillation Division, Inc. | Systems and methods for determining the likelihood of endocardial barotrauma in tissue during ablation |
GB2535657A (en) | 2010-07-13 | 2016-08-24 | Sandhill Scient Inc | Apparatus and method for detecting and measuring condition of esophageal mucosa and indications of gastroesophageal reflux disease |
US8593154B2 (en) | 2010-12-24 | 2013-11-26 | General Electric Company | System and method for artifact suppression in soft-field tomography |
JP2012157463A (en) * | 2011-01-31 | 2012-08-23 | Olympus Corp | Biological impedance measurement device |
US11083391B2 (en) | 2011-06-10 | 2021-08-10 | Cochlear Limited | Electrode impedance spectroscopy |
US8700133B2 (en) | 2012-06-18 | 2014-04-15 | Smart Iv Llc | Apparatus and method for monitoring catheter insertion |
US9597482B2 (en) | 2012-06-18 | 2017-03-21 | Smart Iv Llc | Apparatus and method for monitoring catheter insertion |
US9750417B2 (en) | 2012-06-28 | 2017-09-05 | Volcano Corporation | Connection structures for intravascular devices and associated systems and methods |
CA2877747A1 (en) * | 2012-06-28 | 2014-01-03 | Volcano Corporation | Connection structures for intravascular devices and associated systems and methods |
US20150011856A1 (en) * | 2013-07-03 | 2015-01-08 | Saranas, Inc. | Bleed detection technique |
US10702177B2 (en) * | 2016-08-24 | 2020-07-07 | Biosense Webster (Israel) Ltd. | Catheter with bipole electrode spacer and related methods |
WO2018161067A1 (en) * | 2017-03-03 | 2018-09-07 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Biopsy system for enhanced tissue harvesting |
US11033327B2 (en) * | 2017-10-30 | 2021-06-15 | St. Jude Medical, Cardiology Division, Inc. | Electrophysiology catheter with modular electrode structure |
US11291382B2 (en) | 2018-06-01 | 2022-04-05 | Diversatek Healthcare, Inc. | System and method for detecting and measuring the condition of intraluminal esophageal mucosa |
EP3603721B1 (en) * | 2018-07-31 | 2022-05-11 | Heraeus Deutschland GmbH & Co. KG | Catheter with segmented electrodes and methods of making same |
US11458300B2 (en) | 2018-12-28 | 2022-10-04 | Heraeus Medical Components Llc | Overmolded segmented electrode |
Family Cites Families (60)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US30101A (en) * | 1860-09-18 | Folding-case bedstead | ||
US2008295A (en) * | 1933-12-07 | 1935-07-16 | Smith William | Method of and apparatus for diagnostic analysis |
US2018080A (en) * | 1934-07-09 | 1935-10-22 | Martienssen Oscar | Method of and device for differentiating between geologic strata traversed by bore holes |
US2184511A (en) * | 1937-10-28 | 1939-12-26 | Samuel M Bagno | Method and apparatus for measuring impedance |
US2729211A (en) * | 1950-07-07 | 1956-01-03 | Peter Josef | Device for examining the condition of the stomach |
US2852580A (en) * | 1955-09-26 | 1958-09-16 | Universal Oil Prod Co | Preparation of polyisoolefins |
US3340867A (en) * | 1964-08-19 | 1967-09-12 | Univ Minnesota | Impedance plethysmograph |
USRE30101E (en) | 1964-08-19 | 1979-09-25 | Regents Of The University Of Minnesota | Impedance plethysmograph |
US3480003A (en) * | 1967-02-03 | 1969-11-25 | Battelle Development Corp | Apparatus for measuring esophageal motility |
US4146254A (en) * | 1976-03-31 | 1979-03-27 | Bristol Products, Inc. | Coupler for tubing |
US4224949A (en) * | 1977-11-17 | 1980-09-30 | Cornell Research Foundation, Inc. | Method and electrical resistance probe for detection of estrus in bovine |
US4476872A (en) * | 1980-03-07 | 1984-10-16 | The Kendall Company | Esophageal probe with disposable cover |
WO1982000581A1 (en) | 1980-08-18 | 1982-03-04 | Storey L | Apparatus and method for measuring blood vessel and cardiac characteristics |
SE8103309L (en) | 1981-05-26 | 1982-11-27 | Karolinska Inst | OVERVAKNINGSSOND |
US6010453A (en) | 1982-03-22 | 2000-01-04 | Instrumentarium Corporation | Tonometric catheter combination |
US4643192A (en) | 1982-03-22 | 1987-02-17 | Regents Of The University Of Michigan | Hollow viscus tonometry |
US4437474A (en) * | 1982-07-16 | 1984-03-20 | Cordis Corporation | Method for making multiconductor coil and the coil made thereby |
US4498481A (en) * | 1982-09-28 | 1985-02-12 | Lemke Judith K | Estrus cycle monitoring system |
US4559951A (en) * | 1982-11-29 | 1985-12-24 | Cardiac Pacemakers, Inc. | Catheter assembly |
US4602809A (en) * | 1984-11-21 | 1986-07-29 | General Dynamics, Pomona Division | Miniature O-ringless gas line isolator |
US4729385A (en) * | 1985-10-23 | 1988-03-08 | American Mediscan, Inc. | Probe and method of use for detecting abnormal tissues |
US4690152A (en) * | 1985-10-23 | 1987-09-01 | American Mediscan, Inc. | Apparatus for epithelial tissue impedance measurements |
US4852580A (en) * | 1986-09-17 | 1989-08-01 | Axiom Medical, Inc. | Catheter for measuring bioimpedance |
US4836214A (en) * | 1986-12-01 | 1989-06-06 | Bomed Medical Manufacturing, Ltd. | Esophageal electrode array for electrical bioimpedance measurement |
US4960133A (en) * | 1988-11-21 | 1990-10-02 | Brunswick Manufacturing Co., Inc. | Esophageal electrode |
US5109851A (en) * | 1989-02-06 | 1992-05-05 | Arzco Medical Systems, Inc. | Multiple electrode affixable sheet |
US5158083A (en) | 1989-10-23 | 1992-10-27 | Mountpelier Investments, S.A. | Miniature pco2 probe for in vivo biomedical applications |
US5069223A (en) * | 1990-02-14 | 1991-12-03 | Georgetown University | Method of evaluating tissue changes resulting from therapeutic hyperthermia |
US5074827A (en) * | 1990-08-28 | 1991-12-24 | American Longwall Mining Corporation | Reversible chain conveyor sprocket assembly |
US5456254A (en) * | 1991-02-15 | 1995-10-10 | Cardiac Pathways Corp | Flexible strip assembly having insulating layer with conductive pads exposed through insulating layer and device utilizing the same |
US5280429A (en) * | 1991-04-30 | 1994-01-18 | Xitron Technologies | Method and apparatus for displaying multi-frequency bio-impedance |
US5267564A (en) * | 1991-06-14 | 1993-12-07 | Siemens Pacesetter, Inc. | Pacemaker lead for sensing a physiologic parameter of the body |
US5158429A (en) * | 1991-07-26 | 1992-10-27 | Chiang Chao Cheng | Self-contained cleaning system for smoke exhausters |
US5282840A (en) * | 1992-03-26 | 1994-02-01 | Medtronic, Inc. | Multiple frequency impedance measurement system |
US5922701A (en) | 1992-05-01 | 1999-07-13 | University Of Utah Research Foundation | Method for enhancing or accelerating re-epithelialization or re-endothelialization of a tissue |
US5306052A (en) * | 1992-12-15 | 1994-04-26 | Megushion Kevin D | Tubing union with a torque transfer fitting |
US5585402A (en) | 1992-12-23 | 1996-12-17 | Glaxo Wellcome Inc. | Nitric oxide synthase inhibitors |
US5438985A (en) | 1993-01-25 | 1995-08-08 | Synectics Medical, Incorporated | Ambulatory recording of the presence and activity of substances in gastro-intestinal compartments |
US5355668A (en) * | 1993-01-29 | 1994-10-18 | General Electric Company | Catalyst-bearing component of gas turbine engine |
US5423320A (en) | 1993-04-20 | 1995-06-13 | Argus Critical Care, Inc. | Air tonometry method and apparatus for measuring intraluminal gastrointestinal pCO2 and pO2 |
US5335668A (en) * | 1993-04-30 | 1994-08-09 | Medical Scientific, Inc. | Diagnostic impedance measuring system for an insufflation needle |
US5657759A (en) | 1993-05-13 | 1997-08-19 | Synectics Medical, Incorporated | Measurement of gastric emptying and gastrointestinal output |
US5381790A (en) * | 1993-06-23 | 1995-01-17 | Kanesaka; Nozomu | Electrophysiology apparatus |
US5477854A (en) | 1993-09-16 | 1995-12-26 | Synectics Medical, Inc. | System and method to monitor gastrointestinal Helicobacter pylori infection |
US5454377A (en) | 1993-10-08 | 1995-10-03 | The Ohio State University | Method for measuring the myocardial electrical impedance spectrum |
US6032061A (en) * | 1997-02-20 | 2000-02-29 | Boston Scientifc Corporation | Catheter carrying an electrode and methods of assembly |
US5991650A (en) * | 1993-10-15 | 1999-11-23 | Ep Technologies, Inc. | Surface coatings for catheters, direct contacting diagnostic and therapeutic devices |
US5833625A (en) | 1993-10-21 | 1998-11-10 | Synectics Medical Ab | Ambulatory reflux monitoring system |
US5479935A (en) * | 1993-10-21 | 1996-01-02 | Synectics Medical, Inc. | Ambulatory reflux monitoring system |
US6322518B1 (en) | 1993-12-06 | 2001-11-27 | Heska Corporation | Method and apparatus for measuring cardiac output |
SE512680C2 (en) | 1994-01-24 | 2000-05-02 | Synectics Medical Ab | Methods and systems for determining measurement quantities in liquid by metallic single crystal electrode |
US5578568A (en) | 1994-04-22 | 1996-11-26 | Xoma Corporation | Method of treating conditions associated with intestinal ischemia/reperfusion |
US5810742A (en) | 1994-10-24 | 1998-09-22 | Transcan Research & Development Co., Ltd. | Tissue characterization based on impedance images and on impedance measurements |
WO1996039076A1 (en) | 1995-06-05 | 1996-12-12 | Vanderbilt University | Non-invasive identification of intestinal ischemia from measurement of basic electrical rhythm of intestinal smooth muscle electrical activity |
US5633801A (en) | 1995-10-11 | 1997-05-27 | Fluke Corporation | Pulse-based impedance measurement instrument |
US5807272A (en) | 1995-10-31 | 1998-09-15 | Worcester Polytechnic Institute | Impedance spectroscopy system for ischemia monitoring and detection |
JP3529537B2 (en) * | 1996-03-25 | 2004-05-24 | テルモ株式会社 | Electrode catheter |
US5981590A (en) | 1997-03-17 | 1999-11-09 | Probiotix, Inc. | Oral glutamine in the prevention of neonatal necrotizing enterocolitis and other gastrointestinal mucosal damage |
US6882879B2 (en) | 2000-07-19 | 2005-04-19 | Innovamedica S.A. De C.V. | Impedance spectroscopy system and catheter for ischemic mucosal damage monitoring in hollow viscous organs |
US7646816B2 (en) * | 2001-09-19 | 2010-01-12 | Microsoft Corporation | Generalized reference decoder for image or video processing |
-
2001
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- 2001-07-18 EP EP06015389A patent/EP1707116B1/en not_active Expired - Lifetime
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- 2007-04-12 US US11/787,233 patent/USRE44667E1/en not_active Expired - Lifetime
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- 2011-12-27 US US13/337,529 patent/US8610022B2/en not_active Expired - Fee Related
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ES2381092T3 (en) | 2012-05-23 |
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